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Physiol Behav. 2018 Jul 1;191:37-46. doi: 10.1016/j.physbeh.2018.04.003. Epub 2018 Apr 4.

Hippocampal glial cells modulate morphine-induced behavioral responses.

Author information

1
Department of Physiology, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2
Cognitive Neuroscience Division, Faculty of Education and Psychology, University of Tabriz, Tabriz, Iran.
3
Department of Physiology, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Neurophysiology Research Center, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: nhosseinmardi@sbmu.ac.ir.
4
Neurophysiology Research Center, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
5
Department of Neuroscience, University of Florida, Gainesville, FL 323611, United States.

Abstract

Drugs of abuse cause persistent alterations in synaptic plasticity that is thought to underlie addictive-like behaviors. Although, the perisynaptic glial cells are implicated in metabolic maintenance and support of the nervous systems, accumulating evidence suggests that glial cells exert a modulatory action on synaptic functions and participate in synaptic plasticity. However, it is well-documented that glial cells are associated with the acquisition of rewarding effects of abused drugs. The role of hippocampal glial cells in addictive-like behaviors remains poorly understood. In this study, we investigated the role of hippocampal glial cells in morphine-induced behavioral responses including morphine dependence, tolerance to the antinociceptive properties of morphine, and conditioned place preference (CPP). Male rats received subcutaneous (s.c.) morphine sulfate (10 mg/kg) at an interval of 12 h for 9 days. To suppress glial cells activity, the animals received microinjection of fluorocitrate (FC, a metabolic inhibitor of glial cells) into the CA1 region before each morphine administration. The animals were assessed for morphine dependence by monitoring naloxone hydrochloride-induced precipitation of somatic signs of morphine withdrawal. The tolerance to the antinociceptive effects of morphine and morphine-induced CPP were measured in a separate set of experimental groups. We found animals receiving FC before morphine injection demonstrated a significant reduction in several signs of morphine withdrawal such as freezing, defecation, chewing, explosive running, ptosis, activity, scratching, wet dog shake, and writhing. Inhibition of glial cells caused a significant reduction of tolerance to the antinociceptive effect of morphine. Finally, intra-CA1 administration of FC decreased morphine-induced CPP. Our findings suggest that hippocampal glial cells may be involved in morphine-induced behavioral responses.

KEYWORDS:

CPP; Dependence; Glial cells; Hippocampus; Morphine; Tolerance

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